SESN2 explained

Sestrin-2 also known as Hi95 is a protein that in humans is encoded by the SESN2 gene.^{[1] [2] [3]}

Function

This gene encodes a member of the sestrin family of PA26-related proteins. The encoded protein may function in the regulation of cell growth and survival. This protein may be involved in cellular response to different stress conditions.^[4] The Sestrins constitute a family of evolutionarily-conserved stress-inducible proteins that suppress oxidative stress and regulate adenosine monophosphate-dependent protein kinase (AMPK)-mammalian target of rapamycin (mTOR) signaling. By virtue of these activities, the Sestrins serve as important regulators of metabolic homeostasis.^[5] Accordingly, inactivation of Sestrin genes in invertebrates resulted in diverse metabolic pathologies, including oxidative damage, fat accumulation, mitochondrial dysfunction and muscle degeneration that resemble accelerated tissue aging.^[6]

Ligands

The NMDA receptor antagonist ketamine has been found to activate the mammalian target of rapamycin complex 1 (mTORC1) pathway in the medial prefrontal cortex (mPFC) of the brain as an essential downstream mechanism in the mediation of its rapid-acting antidepressant effects.^[7] NV-5138 is a ligand and modulator of sestrin2, a leucine amino acid sensor and upstream regulatory pathway of mTORC1, and is under development for the treatment of depression. The drug has been found to directly and selectively activate the mTORC1 pathway, including in the mPFC, and to produce rapid-acting antidepressant effects similar to those of ketamine.

See also

• SESN1

Further reading

• Gerhard DS, Wagner L, Feingold EA, etal . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Budanov AV, Sablina AA, Feinstein E, etal . Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD . Science . 304 . 5670 . 596–600 . 2004 . 15105503 . 10.1126/science.1095569 . 2004Sci...304..596B . 27871118 .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Simpson JC, Wellenreuther R, Poustka A, etal . Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing . EMBO Rep. . 1 . 3 . 287–92 . 2001 . 11256614 . 10.1093/embo-reports/kvd058 . 1083732 .
• Wiemann S, Weil B, Wellenreuther R, etal . Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs . Genome Res. . 11 . 3 . 422–35 . 2001 . 11230166 . 10.1101/gr.GR1547R . 311072 .

Notes and References

1. Peeters H, Debeer P, Bairoch A, Wilquet V, Huysmans C, Parthoens E, Fryns JP, Gewillig M, Nakamura Y, Niikawa N, Van de Ven W, Devriendt K . PA26 is a candidate gene for heterotaxia in humans: identification of a novel PA26-related gene family in human and mouse . Hum Genet . 112 . 5–6 . 573–80 . Apr 2003 . 12607115 . 10.1007/s00439-003-0917-5 . 22257894 .
2. Budanov AV, Shoshani T, Faerman A, Zelin E, Kamer I, Kalinski H, Gorodin S, Fishman A, Chajut A, Einat P, Skaliter R, Gudkov AV, Chumakov PM, Feinstein E . Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability . Oncogene . 21 . 39 . 6017–31 . Aug 2002 . 12203114 . 10.1038/sj.onc.1205877 . 7991114 .
3. Web site: Entrez Gene: SESN2 sestrin 2.
4. Lee JH, Bodmer R, Bier E, Karin M . Sestrins at the crossroad between stress and aging . Aging . 2 . 6 . 369–74 . June 2010 . 20606249 . 2919257 . 10.18632/aging.100157.
5. Gong L, Wang Z, Wang Z, Zhang Z . Sestrin2 as a Potential Target for Regulating Metabolic-Related Diseases . Front Endocrinol (Lausanne) . 12 . 751020 . 2021 . 34803916 . 8595836 . 10.3389/fendo.2021.751020 . free .
6. Lee JH, Budanov AV, Karin M . Sestrins orchestrate cellular metabolism to attenuate aging . Cell Metab . 18 . 6 . 792–801 . Dec 2013 . 24055102 . 3858445 . 10.1016/j.cmet.2013.08.018 .
7. Duman RS . Ketamine and rapid-acting antidepressants: a new era in the battle against depression and suicide . F1000Res . 7 . 2018 . 659 . 29899972 . 5968361 . 10.12688/f1000research.14344.1 . free .